Sustained in vitro RNA self-replication achieved
Basic research into the origins of life continues to advance, despite the best efforts of creationists and IDiots to ignore it. Unlike the depictions presented by most evolution deniers, our understanding of prebiotic processes operating on the early Earth is actually quite advanced. Origins of life research is a vigorous field of study today and has progressed far beyond the early Miller-Urey experiments, though you wouldn’t know that from most popular media coverage of the topic. Our picture of the chain of events leading from simple organic molecules to self-replicating biomachines is still fuzzy, but nonetheless that fuzzy picture doesn’t include any blurry images of ghosts, ectoplasm or sky-giants reclining on a cloud and reaching down to engender life with a magic finger.
The consensus model in modern origins of life research is the RNA world model, in which life started as a simple RNA mechanism that could replicate itself, only later accumulating the complex bells and whistles (e.g. DNA, thousands of enzymes) that we see in the LUCA. The earliest life on Earth would have needed to operate without all those bells and whistles, using only a simple and robust complex of only a few molecules to get going. Some RNA sequences can catalyze their own replication in the absence of other enzymes, however up until now RNA studies have been unable to demonstrate sustained replication. No longer.
A new study by Tracey Lincoln and Gerald Joyce, both at the Scripps Institute of Oceanography, demonstrates in vitro RNA self-replication that sustains itself indefinitely. This is big news. As Phil Plait would say, this is HUGE! The new study – which was recently published online in Science magazine – shows that RNA molecules can be made to continuously generate copies of themselves in the presence of raw components. If the results hold up under peer review and independent confirmation, this study will be a giant step forward in demonstrating a plausible chain of events that could have led from geochemistry to biochemistry on the early Earth.
The Lincoln and Joyce study shows that at least two molecules of RNA can operate as a functional unit, binding together temporarily to form a working template that automatically builds a copy of itself. Once the copy is made the individual RNA subunits separate, but can recombine ad infinitum to generate further copies, as long as enough raw material is present. In their experiments the authors supplied different “starter” RNA strands having a variety of sequences, but all were relatively short chains of only a few bases. They found that most strand sequences were poor self-replicators, but a few particular sequences tended to naturally stand out in their ability to combine and replicate, and over time those particular RNA sequences would come to dominate the experimental system. With each replication event the most efficient RNA configurations would out-compete less efficient sequences, until there were only a few clear winners.
The results show that RNA can undergo a kind of molecular evolution by natural selection, where the selection pressure is the relative efficiency of chemical reactions among competing RNA sequences. Where two or more RNA molecules link up and form a particularly efficient replicator – simply by virtue of the laws of physical chemistry acting on the geometry of molecular bonds in the RNA construct – that particular RNA design will tend to dominate over others as it doubles itself again and again geometrically. Less efficient molecular designs cannot replicate fast enough to keep up, and their components eventually fall apart or are scavenged by more stable molecular bond arrangements in the RNA copying contest. Mutant mis-copies add additional diversity, and because chemical reactions occur in femtoseconds a wide variety of mutants can quickly emerge to push the replication efficiency higher and higher. It’s an elegant case of Mindless Design… blind chemistry pushing molecules up Mount Improbable.
I’ve discussed the idea of RNA molecular evolution previously in this blog, and it’s fascinating to see a working example of this process clearly demonstrated. The Lincoln and Joyce results show that in a complex system of competing RNA variants, some variants will naturally “cooperate” to yield spectacular results. The study also addresses a nagging problem in origins of life research, where modern cellular RNA units are typically very long – thousands of bases – but the longest in vitro self-replicating RNA sequences found until now were very short. Lincoln and Joyce demonstrate that the best copiers don’t have to be single molecules – they can be temporary associations of subunits – neatly circumventing the problem of life’s needing to start with giant RNA strands. Principal actors can co-opt smaller “helper” units, laying the groundwork for a system of core RNA units and satellite enzymes.
Thanks to Dr. Steven Novella’s Neurologica Blog for the heads-up on this new study. I now owe Dr. Novella a White Russian, which I shall supply him at TAM 7. So let it be written, so let it be done.